Turkey has several endemic edible plant species having health benefits. Polygonum sivasicum is widely consumed as fresh or dried throughout the year by rural people in Sivas province. This study aimed to reveal the health benefits of P. sivasicum and to assess the effects of different drying methods on nutritional, phytochemical, and biological activities. Polygonum sivasicum leaves were collected from Sivas province and dried freeze, oven, microwave, and shade treatments. For each sample, total phenolic content and profile, antioxidant activity, mineral analysis and antibacterial properties were investigated. The highest phenolic content and antioxidant activity were observed in freeze-dried samples (P < 0.05). Rutin was detected as a major phenolic compound, followed by chlorogenic acid, kaempferol-3-O-glucoside, iso-rhamnetin-3-O-glucoside, ferulic acid, luteolin, and caffeic acid, respectively. The P. sivasicum leaves seem to be rich in potassium, phosphorus, and magnessium. P. sivasicum extracts showed antimicrobial activity against S. aureus and L. innocua depending on the extraction solvent. Freeze-drying method can be used as a convenient drying method due to preserve the total phenolic content and individual phenolic compounds.